Congenital dyserythropoietic anemia types Ib, II, and III: novel variants in the CDIN1 gene and functional study of a novel variant in the KIF23 gene.

Manuel Méndez, María Isabel Moreno-Carralero, Valeria L Peri, Rafael Camacho-Galán, José M Bosch-Benítez, Jorge Huerta-Aragonés, Jorge Sánchez-Calero-Guilarte, María Belén Moreno-Risco, Juan Manuel Alonso-Domínguez, María José Morán-Jiménez

Journal: Annals of hematology 2021;100(2):353-364

PMID: 33159567

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Abstract

Congenital dyserythropoietic anemias (CDA) are disorders characterized by ineffective erythropoiesis and morphological anomalies in erythrocytes and erythroblasts. The purpose of this study is to identify the gene variants in patients diagnosed with CDA. We analyzed five unrelated patients and two siblings with a targeted panel of genes to CDA: CDAN1, CDIN1, SEC23B, KIF23, KLF1, and GATA1 genes. We found three novel variants in the CDIN1 gene (p.Leu136Val, p.Tyr247Cys, and p.Ile273Thr), four known variants in the SEC23B gene (p.Arg14Trp, p.Arg554Ter, p.Asp239Gly, and p.Ser436Leu), and one novel variant in the KIF23 gene (p.Leu945Trpfs*31). The in silico analysis of novel variants predict that they are pathogenic and, the in vitro study confirms the functional impact of the KIF23 variant on the protein location.

Address: Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain.; Servicio de Hematología, Complejo Hospitalario Insular-Materno Infantil, Las Palmas de Gran Canaria, Spain.; Servicio de Anatomía Patológica, Hospital Universitario Doctor Negrín, Las Palmas de Gran Canaria, Spain.; Servicio de Pediatría, Sección de Oncología y Hematología Pediátricas y del Adolescente, Hospital Materno-Infantil Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.; Servicio Hematología, Hospital Móstoles, Madrid, Spain.; Servicio de Hematología y Hemoterapia, Hospital Materno Infantil, Badajoz, Spain.; Servicio de Hematología, Fundación Jiménez Díaz, Grupo de Hematología Experimental, Fundación Instituto de Investigación Sanitaria-Fundación Jiménez Díaz (IIS-FJD), Madrid, Spain.; Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain. [email protected].

DOI: 10.1007/s00277-020-04319-5

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MeSH Terms: Adolescent, Adult, Amino Acid Substitution, Anemia, Dyserythropoietic, Congenital, Child, Female, Humans, Male, Microtubule-Associated Proteins, Mutation, Missense